A principal objective is to discover the cause of the obesity - the location and nature of the metabolic or developmental error produced by two doses of the recessive fatty gene. Many features of the fatty syndrome may be regarded as consequences of attained obesity. It is clear from the study of various obesities that there is a characteristic obese metabolism with various common abnormal features. These are in themselves worthy of study and such study is also an objective. A truly causative factor should coexist with obesity right back to the earliest age at which obesity can be demonstrated, whereas consequences of obesity should gradually fade away. This is the technique relied upon for isolating the causative factor; abnormalities found in the fatty are studied in the preobese and early obese stage. Under intensive study, partly in collaboration with other investigators: (1) Insulin action and status in the fatty. Probable conclusions are that hyperinsulinemia is the necessary enabling agent for fat deposition, and is invoked by the unknown primary causative factor. (2) Fat cell proliferation is apparently out of control in the fatty, but it is not clear for technical reasons how early in life the signal for this excessive proliferation is established. (3) Skeletomuscular stunting is the earliest abnormality yet demonstrated, being present at 2 weeks of age when fattening is just beginning, but before the advent of hyperinsulinemia. This stunting responds to growth hormone (GH), which also greatly reduces the obesity. Because of the probable role of amino acid supply in control by GH, and because of the observed effects of food intake (AA supply?) on the degree of stunting, amino acid levels in muscle and plasma with and without GH are under study. (4) GH action in the fatty; simultaneous effects on growth and intermediary metabolism.